Metabolic and Adipokine Profile of Chinese Patients With Nonalcoholic Fatty Liver Disease

Wong, Vincent Wai‐Sun; Hui, Alex; Tsang, Steven Woon–Choy; Chan, Joyce; Tse, Ada Mei–Ling; Chan, King-Man; So, Wing‐Yee; Cheng, A. Y. S.; Ng, Wing–Fung; Wong, Grace Lai–Hung

doi:10.1016/j.cgh.2006.06.011

Cited by 180 publications

(160 citation statements)

References 50 publications

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“…This is a perplexing result as previous investigators have shown elevated levels of TNF-␣ in NASH patients, 26 and a subsequent decrease in TNF-␣ with improvement in insulin resistance. 27 In our trial, TNF-␣ levels in four subjects were elevated significantly at the end of the study compared with baseline despite improvement in adiponectin, serum ALT, and NAS score in all cases.…”

Section: Discussionmentioning

confidence: 85%

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Fecht²,

et al. 2008

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The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index ‫؍‬ >27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 ؎ 9.0 (standard deviation) years and mean body mass index was 36.4 ؎ 6.3 kg/m 2 . Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of >5% body weight (n ‫؍‬ 24) compared to <5% body weight (n ‫؍‬ 17) correlated with improvement in insulin sensitivity (P ‫؍‬ 0.001) and steatosis (P ‫؍‬ 0.015). Comparing subjects who lost >9% of body weight (n ‫؍‬ 16), to those that did not (n ‫؍‬ 25), improved insulin sensitivity (P < 0.001), adiponectin (P ‫؍‬ 0.03), steatosis (P ‫؍‬ 0.005), ballooning (P ‫؍‬ 0.04), inflammation (P ‫؍‬ 0.045), and nonalcoholic fatty liver disease activity score (P ‫؍‬ 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P ‫؍‬ 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >9% also achieved improved hepatic histologic changes. (HEPATOLOGY 2009;49:80-86.)

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Section: Discussionmentioning

confidence: 85%

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Fecht²,

et al. 2008

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“…The negative predictive values (100% and 81%, respectively) were also high, especially because the prevalence of advanced disease is lower in Asian countries. 29 However, the specificities dropped below 15%. Some cases of NA-FLD with severe fibrosis and early cirrhosis may even have a drop in ALT level as the disease reaches a burnt-out stage.…”

Section: Discussionmentioning

confidence: 97%

“…This echoes previous cross-sectional studies that obesity and diabetes were the most important factors associated with histological severity. 18,29,33 Metabolic factors are more important than the ALT level in predicting NASH and significant fibrosis. Obesity and the history of impaired fasting glucose or diabetes were independent factors associated with NASH, while age, fasting glucose and insulin resistance (HOMA-IR) were independent factors associated with significant fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Some cases of NA-FLD with severe fibrosis and early cirrhosis may even have a drop in ALT level as the disease reaches a burnt-out stage. 29 Based on our reported specificities, although it is possible to observe patients with ALT below 0.5 · ULN, it is not reasonable to advise liver biopsies for every patient with ALT above this cutoff because many would still have simple steatosis only. Further work on non-invasive evaluation of NAFLD is urgently needed.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

Wong

Tsang

et al. 2009

Aliment Pharmacol Ther

108

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“…34 In fact, growing evidence indicates that NASH is a consequence of disturbances in the signaling pathways originating from cytokines and adipokines, which can directly or indirectly (through IR) influence its pathogenesis or progression. [35][36][37] Unfortunately, molecular pathways linking adipokines with their nuclear and cytoplasmic targets are largely unknown, so the profiling of these networks awaits the characterizations of corresponding pathways. This study is a step in that direction, because many phosphorylation events differentiating progressive and non-progressive forms of NAFLD also affect adipokine production and signaling.…”

Section: Discussionmentioning

confidence: 99%

A systems biology approach to the pathogenesis of obesity-related nonalcoholic fatty liver disease using reverse phase protein microarrays for multiplexed cell signaling analysis

et al. 2007

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Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Omental adipose tissue, a biologically active organ secreting adipokines and cytokines, may play a role in the development of NAFLD. We tested this hypothesis with reverse-phase protein microarrays (RPA) for multiplexed cell signaling analysis of adipose tissue from patients with NAFLD. Omental adipose tissue was obtained from 99 obese patients. Liver biopsies obtained at the time of surgery were all read by the same hepatopathologist. Adipose tissue was exposed to rapid pressure cycles to extract protein lysates. RPA was used to investigate intracellular signaling. Analysis of 54 different kinase substrates and cell signaling endpoints showed that an insulin signaling pathway is deranged in different locations in NAFLD patients. Furthermore, components of insulin receptor-mediated signaling differentiate most of the conditions on the NAFLD spectrum. For example, PKA (protein kinase A) and AKT/mTOR (protein kinase B/mammalian target of rapamycin) pathway derangement accurately discriminates patients with NASH from those with the non-progressive forms of NAFLD. PKC (protein kinase C) delta, AKT, and SHC phosphorylation changes occur in patients with simple steatosis. Amounts of the FKHR (forkhead factor Foxo1)phosphorylated at S256 residue were significantly correlated with AST/ALT ratio in all morbidly obese patients. Furthermore, amounts of cleaved caspase 9 and pp90RSK S380 were positively correlated in patients with NASH. Specific insulin pathway signaling events are altered in the adipose tissue of patients with NASH compared with patients with nonprogressive forms of NAFLD. Conclusion: These findings provide evidence for the role of omental fat in the pathogenesis, and potentially, the progression of NAFLD. (HEPATOLOGY 2007;46:166-172.)

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Metabolic and Adipokine Profile of Chinese Patients With Nonalcoholic Fatty Liver Disease

Cited by 180 publications

References 50 publications

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Metabolic and histological features of non‐alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

A systems biology approach to the pathogenesis of obesity-related nonalcoholic fatty liver disease using reverse phase protein microarrays for multiplexed cell signaling analysis

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